The present program project is concerned with studies of erythrocytes and hemoglobin, its properties as a protein and its function in red cell in vivo and in vitro. Hemoglobin association reactions are being studied with calorimetric, spectrophotometric and isotope exchange kinetic methods. The thermodynamics of hemoglobin interaction with ligand and the role of solvent is studied both experimentally and from a theoretical point of view, with special attention given to the polymerization process of hemoglobin S. In case of red cells, special attention is given to membrane lesions due to changes of electrolyte balance following cell damage by sickling. Electronmicroscopic studies are being carried out of the red cell, its membrane and the hemoglobin aggregates appearing in sickle cells. EM studies are supported by measurements of the elasticity and deformability of the red cell. In addition, the effect of chemical modifiers of hemoglobins is being investigated by most of the above mentioned methods.